The neurobiology of social attachment remains relatively uninvestigated despite its relevance to psychiatry, psychology, and developmental psychobiology. Recent studies with a monogamous rodent, the prairie vole (Microtus ochrogaster), have provided a reliable behavioral index for quantitative studies of social attachment. Prairie voles exhibit mating-induced pair bonding which is indicated by a sustained preference for a mate versus a conspecific stranger (partner preference). Previous research has demonstrated the role of dopamine (DA) in this process. DA is released in the nucleus accumbens (NAcc) during mating, DA acts on D2-type receptors in the NAcc shell to facilitate partner preference formation, and Dl- and D2-type receptors have opposite modulation of pair bonding. In addition, neuropeptide oxytocin (OT) in NAcc has also been implicated in the regulation of pair bonding. Although these data reveal the importance of NAcc DA and OT in pair bond formation, little is known about the intracellular mechanisms and interactions of DA and OT underlying pair bonding. In the present application, we propose four studies to systematically investigate the role of the cAMP second messenger cascade and interactions of DA and OT in NAcc in the regulation of pair bonding in male prairie voles. In Specific Aim 1, we will examine the activity of the cAMP cascade during mating and pair bond formation as well as during D2- type receptor activation in the prairie vole's NAcc. In Specific Aim 2, we will investigate the effects of the G protein/ cAMP manipulation in NAcc on partner preference formation. In Specific Aim 3, we will determine the role of NAcc OT on pair bonding and on the cAMP activity. In Specific Aim 4, we will investigate the effects of DA and OT interactions in NAcc on partner preference formation and on the cAMP cascade activity. Together, these studies should provide a comprehensive understanding of the intracellular cAMP cascade underlying DA-OT interactions in NAcc in the regulation of pair bonding. Successful completion of these studies will significantly further our understanding of neurobiology of social attachment and therefore provide valuable information regarding disorders associated with inability to form social bonds in humans.